This project seeks to evaluate the factors regulating substrate (glucose, amino acid) metabolism in normal physiology, in diabetes and in obesity. The project consists of five major areas of investigation: 1. Determination of the relation between alterations in insulin binding and insulin action in non-obese maturity onset diabetics. 2. An examination of the effects of continuous low dose insulin infusion on glucose kinetics in normal subjects and diabetics. 3. Evaluation of the effects of portable, pre-programmed insulin delivery system on blood glucose control in insulin-dependent diabetics ("open look", subcutaneous, "artificial pancreas"). 4. Comparison of the effects of hypocaloric pure protein diets and isocaloric mixed diets (protein plus carbohydrate) on the metabolic response and on weight loss in obese subjects. 5. Examination of the role of gut factors in regulating hepatic glucose metabolism using dogs with catheters implanted in the portal and hepatic veins.